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Study questions expected link between farming and evolution of immune system

Study questions expected link between farming and evolution of immune system

Researchers have long theorized that cultural shifts thousands of years ago from hunting and gathering to agriculture and living in permanent settlements spurred an increase in diseases like smallpox and measles. Compared to hunter-gatherers, farmers stayed put, living close to one another and their animals.

It’s hypothesized this made it easier for viruses and bacteria to spread among humans or from animals to people. Consequently, it might be expected that the immune systems of people from these farming populations would show more signs of positive natural selection through adaptation to these pathogen conditions.

A new study published in Nature Ecology & Evolution by University of Chicago Medicine genetic researcher Luis Barreiro shows that the opposite is true when comparing farmers and hunter-gatherers in southwest Uganda. Instead, the immune systems of hunter-gatherers showed more signs of positive natural selection, in particular among genes involved in the response to viruses.

“It’s the complete opposite of what we expected, based on the longstanding hypothesis that the advent of agriculture increased selective pressures imposed by pathogens in human populations,” said Barreiro, the study’s senior author and an associate professor in the University’s section of genetic medicine.

Researchers studied the blood of the Batwa, a rainforest hunter-gatherer population from southwest Uganda, and compared it to the blood of their Bantu-speaking agriculturalist neighbors, the Bakiga.

“It’s the complete opposite of what we expected, based on the longstanding hypothesis that the advent of agriculture increased selective pressures imposed by pathogens.”

—Assoc. Prof. Luis Barreiro

White blood cells from the two groups were isolated and exposed to Gardiquimod, which mimics a viral infection, and lipopolysaccharide, which simulates a bacterial infection.

The authors observed increased divergence between hunter-gatherers and agriculturalists in their immune responses to viruses, compared to that for bacterial infections. A significant proportion of these differences were shown to be under genetic control and affected by recent positive natural selection.

“These findings suggest that differences in viral exposure may have been key contributors to the divergence in immune responses between the Batwa and the Bakiga populations, said co-author George Perry, an associate professor of anthropology and biology at Penn State University.

This study marks the first time the immune systems of hunter-gatherers and farmers have been compared to help researchers understand how agriculture may have impacted our immune system. The team spent three years establishing connections and discussing mutual research interests with the Batwa and Bakiga prior to collecting any blood samples. The Batwa have lived in settlements along the edges of the Bwindi Impenetrable Forest since 1991, after being displaced from the rainforest. As a result, the researchers limited their Batwa blood samples to individuals born before 1991 who had actually lived in the forest.

Since collecting the blood samples, the researchers have returned to Uganda multiple times to present the results of their research with these communities.

The researchers cautioned that the Batwa and Bakiga populations likely diverged more than 60,000 years ago, long before the origination and spread of agriculture in Africa. They hope to soon begin similar follow-up studies on additional pairs of hunter-gatherer and farming populations in other areas of the world.

Additional authors include Genelle Harrison and Erwin Schurr of McGill University, Joaquin Sanz and Jonathan Boulais of Université de Montréal, Lluis Quintana-Murci of Institut Pasteur, Jean-Christophe Grenier, Anne Dumaine and Vania Yotova of CHU Sainte-Justine Research Center, Yumei Leng, Stephen Elledge and Michael Mina of Harvard Medical School, Christina Bergey of Penn State and Samuel Nsobya of Makerere University.

Citation: Genelle F. Harrison et al. “Natural selection contributed to immunological differences between hunter-gatherers and agriculturalists.” Nature Ecology & Evolution July 29, 2019. DOI: 10.1038/s41559-019-0947-6

Materials provided by University of Chicago

boy treated with gene therapy

Scientists cure “bubble boy” disease with help of an improved gene therapy

Researchers declared that ten newborn children with a rare genetic disorder, the “bubble boy disease” were cured with the help of gene therapy.

With the help of this treatment, the babies have been cured of the disorder without any side effects or post-treatment complications. Scientists carrying out research hoped for this result for decades but had always received setbacks until now.

In 2003, researchers tried to use gene therapy for treating Severe Combined Immunodeficiency Disease, but they stopped midway as it was detected that the therapy gave them cancer. The present treatment does not come with any such dangerous side effects and scientists hope that it can be used for other rare diseases too such as sickle cell disease.

Children born with SCID did not have a properly working immune system and without receiving any treatment they did not even make it past their first birthday. Even simple illnesses such as common cold were fatal for these children. These children were kept in very protected environments and it gave rise to the name “bubble boy“. However, a boost in the mortality rate has been observed recently owing to the advanced detection tests and treatments such as bone marrow transplants. Unfortunately, even these treatments have complications and they make the patients dependent on regular dosages of immunoglobulin.

The latest gene therapy has been developed by St. Jude Children’s Research Hospital and UCSF Benioff Children’s Hospital based in San Francisco. The therapy rectifies the genetic defects which are there in the DNA of the babies just after they are born, which helps the body to develop the parts of the immune system that are missing.

After the extraction of blood stem cells from the bone marrow of the infants, researchers used a virus as a means of transport to send the corrected version of the defective gene to the stem cells of the patients. The rectified cells were reinfused into the body of the patients where the proliferation of the cells took place to grow healthy immune cells.

Scientists took special care in not enabling the genes which cause cancer, so they added “insulators” with the virus such that surrounding genes would not get affected when the virus is inserted into DNA. Apart from this, the patients were also given chemotherapy to a small extent for clearing the existing cells from the bone marrow so that proliferation of the corrected cells can occur in a better way.

It was an emotional day for the announcement at the St. Jude Children’s Research Hospital, as the team leader Brian Sorrentino had spent his last days fighting against his cancer to finish the work on the treatment.

Urine cultured on Oxoid Brilliance UTI Agar plate

Harnessing Zinc would help to cure UTI without antibiotics

UTIs are one of the prominent bacterial infections across the globe, with about 150 million cases each year, and can lead to serious health problems like chronic kidney infection (pyelonephritis) and sepsis.

Recently in a study, it was found that zinc can play a vital role in the development of new non-antibiotic treatment strategies for UTIs using our immune system.

The study was done by the researchers, including members of the IMB (Institute for Molecular Bioscience) – Professor Matt Sweet, Dr. Ronan Kapetanovic and Claudia Stocks, and members of UQ’s School of Chemistry and Molecular Biosciences  – including Professor Mark Schembri and Dr. Minh-Duy Phan, examined how our immune system uses zinc to fight against bacterial infections.

“We confirmed by direct visualization that cells in our immune system known as macrophages deploy zinc to clear bacterial infections,” said Dr. Minh Duy from UQ’s School of Chemistry and Molecular Biosciences.

“We found that, compared to non-pathogenic bacteria, UPEC can evade the zinc toxicity response of macrophages, but these bacteria also show enhanced resistance to the toxic effects of the zinc.
These findings give us clues to how our immune system battles infections, and also potential avenues to develop treatments, such as blocking UPEC’s escape from zinc to make it more sensitive to this metal.”

The team developed new systems to track and analyze the insertion of zinc in macrophages, with this work just published in Proceedings of the National Academy of Sciences USA (PNAS USA).

They found that, compared to non-pathogenic E. coli, UPEC has a two-pronged strategy to survive the body’s immune response. It can prevent the delivery of zinc by hiding within the macrophage itself.

E Coli Bacteria

Colorized scanning electron micrograph of Escherichia coli, grown in culture and adhered to a cover slip. Source: https://www.flickr.com/photos/niaid/16578744517/

“We knew that UPEC can escape from the normal digestion pathway of the macrophage.
Our latest results show that UPEC can also avoid the delivery of zinc by hiding in different niches in these cells,” Dr. Kapetanovic said.
“It’s now clear that UPEC’s ability to occupy these specific compartments is an important factor in allowing it to spread through the body to cause severe disease.”

But evasion isn’t UPEC’s only trick. The team also found that UPEC has an enhanced ability to resist zinc toxicity.

“When we looked at UPEC, we found that they can also resist the toxic effects of zinc better than other bacteria,” Dr. Kapetanovic said.
“Taken together, these results may provide some potential avenues to develop treatments to combat UPEC and the diseases it causes, such as UTIs and sepsis. For example, blocking UPEC’s escape from zinc to make it more sensitive to this metal could help the body fight back.”

Professor Schembri and Dr. Phan used a technology called TraDIS to identify the full suite of UPEC genes involved in zinc resistance. Some of these genes had previously been explored, but a large number of others had not been explored for their involvement in protecting against zinc pressure.

Dr. Phan said, “The TraDIS analysis had given the researchers a map of which genes they could potentially target to make them more sensitive to zinc”. The team particularly focused on a type of cell called macrophage.

“Macrophages are key immune cells in the body. They digest and destroy a variety of different pathogens, have many strategies to do this, some of which are very well known and some that we’re really only discovering now.

One such recently discovered macrophage antimicrobial response uses zinc poisoning to kill bacteria, so we investigated how macrophages deploy zinc against UPEC.” said Miss Stocks.

“In creating this tool, we’ve not just found out more about E. coli, but have also created a model to study different types of bacteria, bringing us closer to not only understanding our immune system better but also to creating therapies for a range of infectious diseases.

Macrophages deploy zinc against persistent bacteria that aren’t necessarily being cleared by normal mechanisms, for example, Mycobacterium tuberculosis, Salmonella and Streptococcus; all bacteria that can cause chronic infections,” Miss Stocks said.

The new research doesn’t just have after effects for UPEC and  UTIs they cause. The team has also developed zinc sensors that could be used to study a variety of disease-causing bacteria.